A sphingosine-1-phosphate receptor 1 (S1P1) antagonist is expected to be an anti-angiogenic compound; however, there are few reports that demonstrated that a S1P1 inhibitor improved the disease state in an angiogenic animal model. Since we determined that a prototype S1P1 antagonist was an in vivo angiogenesis inhibitor, we developed the derivatives to… (More)

We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a… (More)

We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position… (More)

A series of Sodium 4-[(4-butoxyphenyl)thio]-2'-substituted-1,1'-biphenyl-3- sulfonates were identified as functional sphingosine-1-phosphate (S1P) antagonists with selectivity for the S1P(1) receptor subtype starting from chemical lead 2, which was found while screening our in-house compound library. We performed chemical modifications on each regional… (More)

S1P(3)-sparing S1P(1) agonists have attracted attention as a suppressant of autoimmunity with reduced side effects. Our synthetic efforts and extensive SAR studies led to the discovery of 10b named CS-2100 with the EC(50) value of 4.0 nM for human S1P(1) and over 5000-fold selectivity against S1P(3). The in vivo immunosuppressive efficacy was evaluated in… (More)